Triggered “On/off” Luminescent Polypeptide Bowl‐Shaped Nanoparticles for Selective Lighting of Tumor Cells

Abstract Functional polymeric nanoparticles, especially those with anisotropic structures, have shown significant potential and advantages in biomedical applications including detecting, bioimaging, antimicrobial and anticancer. Herein, tetraphenylethylene (TPE) and azobenzene modified polypeptides of poly(( _L ‐glutamic acid) tetraphenylethylene‐ stat ‐( _L ‐glutamic acid)) (P(GATPE ₉ ‐ stat ‐GA ₂₅ )) and poly(( _L ‐glutamic acid) azobenzene‐ stat ‐( _L ‐glutamic acid)) (P(GAAzo ₅ ‐ stat ‐GA ₂₉ ) are synthesized, which self‐assemble into bowl‐shaped nanoparticles (BNPs) with controlled diameter, opening size and fluorescent property individually, or by co‐assembly. Due to the quenching effect of azobenzene, the fluorescence of the coassembled BNPs is completely inhibited. Upon incubated under reduction environment, the fluorescence of the BNPs is re‐excited owing to the reduction or break of azo bonds. Benefiting from the high‐level azo reductase in hypoxic liver cancer cells comparing to normal liver cells, the quenched BNPs exhibit pronounced fluorescence signal in human hepatoma (HepG2) cells under hypoxic condition, demonstrating the high efficiency of the reduction‐responsive luminescent BNPs for selective screening of tumor cells. In addition, it is also found that a proper opening size promotes the cellular uptake of the BNPs even with size up to micron. Overall, this study provides a fresh perspective in the controlled preparation of anisotropic polymeric nanoparticles and high efficient cancer cell screening.